Immune mechanisms and predictive biomarkers related to neoadjuvant immunotherapy response in stage III melanoma

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Figueiredo, Amanda Braga ; Barros e Silva, Milton Jose ; de Britto Evangelista, Guilherme Ferreira ; de Lima Galdino, Nayane Alves ; de Melo Kuil, Larissa ; Santos, Iasmim Polido ; Morais, Katia Luciano Pereira ; Cavalcanti, Clara Maciel ; Moredo, Luciana Facure ; Duprat-Neto, Joao Pedreira ; Gollob, Kenneth J.

• Document type: Journal article
• Source: HELIYON; v. 10, n. 12, p. 11-pg., 2024-06-30.

Abstract

The treatment for stage III melanoma has advanced significantly, nevertheless, a substantial proportion of patients experience relapse. Neoadjuvant immune checkpoint blockade has emerged as a promising approach, allowing early micrometastatic disease treatment, reduction of tumor burden before surgery, and enhanced tumor-specific T-cell responses. However, not all patients respond to treatment, highlighting the need for understanding immune mechanisms behind failure and identification of predictive markers. Here we performed a robust evaluation of systemic and tumoral immune profiles in a well-defined cohort of advanced melanoma patients treated with immune checkpoint inhibitors. Elevated CTACK and CXCL9 chemokines pretreatment suggested their potential as predictive tools for treatment response. Furthermore, CD95 expression in CD8+ T lymphocytes surfaced as a favorable prognostic indicator, while PD-1, CD161, and PD-L2 exhibited correlations with worst outcomes. These findings shed light on the intricate interplay between immune markers and melanoma response to neoadjuvant immune checkpoint therapy, offering insights into personalized treatment strategies. (AU)

• FAPESP's process: 21/00408-6 - Center for Research in Immuno-Oncology (CRIO)
• Grantee: Kenneth John Gollob
• Support Opportunities: Research Grants - Research Centers in Engineering Program
• FAPESP's process: 18/06409-1 - A prospective study to elucidate systemic and tumor microenvironment immunoregulatory networks related to anti-PD1 treatment failure in stage IV NSCLC and melanoma patients
• Grantee: Amanda Braga de Figueiredo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral